controling lipid oxidation

8/10/2019 Controling Lipid Oxidation

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ROS & Health


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Reactive Oxygen Species ROS

ROS are free radical containing molecules

Highly reactive

Generated by smoking, irradiation,inflammation, glycoxidation, AND

Lipid Oxidation

Linked to disease & aging processes

Lee et al 2004. Comp Reviews Food Sci. Safety 3:21-33


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ROS and Health

Oxidative stress increase- caused byantioxidant deficient diets and/or increased

production of ROS

Balance between ROS level and anti-oxidative

capacity shifted

Increased level of ROS results in: DNA and Protein modification

Sets stage for disease & degeneration


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Principle Factors

Superoxide anion (O2

) - from mitochondrial

ET reductions of O2water

Hydroxyl radical (OH) - in the presence of

Cu/FeO2

+ H2O2OH + OH-+O2

Hydrogen peroxide (H2O2) - from SOD

Singlet oxygen (1O2) - from photosensitizer

(chlorophyll, myoglobin, hemoglobin) + O2


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Additional Factors

Peroxyl (ROO) & Alkoxyl (R) radicals - from UVlight, Cu/Fe, O2

Nitric oxide (NO) and dioxide (NO2) radicals -

from R enzymatically, or peroxy radical + NO

Peroxynitrite (OONO-) from NO and superoxide

anion

Lipoxygenase- activated by peroxide oxidation of Fe(+2+3), especially active with free PUFA

(liberated by lipase action)


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Lipid Oxidation & Aging

Cell membranes are primary targets (high inunsaturated lipid)

Products of lipid oxidation reactions

Malonaldehyde Oxidized LDL

Oxidized CholesterolContributes to age-related illness - diabetes,

atherosclerosis, inflammation


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Oxygen Species-Lewis Structures


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Lipid Free Radical


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Protein Oxidation

ROS attack proteins

Hydroxyl Radical

Lipid oxidation products(e.g., aldehydes)


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Nucleic Acid Modification

Modification by OH radical results in

8-Hydroxydeoxyguansine

GA (= a mutation)


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Neutraceuticals

Compounds with biological importanceabove and beyond their nutritional value

Purported benefits Disease prevention

Slowing of aging

Reduction of ROS


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Antioxidant Neutraceuticals

Antioxidative enzymesHydrogen donating neutraceuticals

Metal Chelators

Singlet Oxygen quenchersTocopherols

Ascorbates

CarotenoidsPolyphenols

Lipoic acids


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Antioxidative Enzymes


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AntioxidantE

nzymes


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Tocopherol

Tocopherol activity linked to Reduction of heart disease

Delay of Alzheimers

Prevention of cancer


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Ascorbic acid

Associated with: Prevention of heart disease

Prevention of cancer

Ascorbates are excellent H donors

(terminate free radical reactions)


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Synergistic Action Ascorbate-Tocopherol


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CarotenoidsAssociated with prevention of:

Atherosclerosis

Macular degeneration

Colorectal cancer

Mechanism of action Highly efficient quencher of singlet oxygen

H donation to free radical

Forms without ionone ring more potentantioxidant activity


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Carotenoids


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Flavonoids


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Isoflavonoids

Soybean

Genistein high conc

Glycosides

AglyconesAntiox activity as

H donor

Metal Chelating


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FRS-Resonance Delocalization


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Lipoic Acid

Both forms scavenge ROSRegenerate GSH

Prevent oxidative damage to proteins

H donor

Metal chelator


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3,5,4-trihydroxystilbene (phytoalexin)

Flavonoid polyphenol

Inhibits fungal infection in plants

The French Paradox

Resveratrol

King et al. Comp. Rev. Food Sci. Food Safety. 2006. 5: 65-70.


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Resveratrol Foods

Numerous plants Extracts of eucalyptus, spruceherbal

medicines

Peanuts

Grapes


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Resveratrol Forms

cis

trans

Glycosides (Piceid)


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Wine Fermentation

Resveratrol associated with skins

Trans isoform more abundant than cis

Piceid forms decrease with fermentation

Extraction efficiency increases with

ethanol content


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Resveratrol Antioxidant Activity

Better hydroxy radical scavenger capacity

than vitamin C or E

Delay or inhibit oxidative stress linked to

macular degeneration

Reduces lipid peroxidation, oxidation of

LDL, (conditions linked to atherosclerosis)


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Resveratrol & Cardiovascular Health

Inhibits platelet aggregation (Limits LPS +

thrombin-stimulated platelet adhesion)

Vaso-relaxation results in lower blood

pressure


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Resveratrol Anticancer Activity

Anti-proliferative effects

Inhibits tumor progression in vitro

Induces apoptosis

Piceatannol (commercial analog)


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Anti-inflammatory Effects

Inhibits inflammatory cytokine action

Tumor Necrosis Factor- (TNF-)

Interleukin-1

(IL-1

)COX-2

May be effective in controlling diabetes


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Phytoestrogenic Activity

Resveratrol is structurarly similar to

Diethylstilbestrol (DES)

Estrogenic activity linked tocardio-protective effect

Inhibits AGE product damage


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Signal Transduction Modulator

Resveratolsbeneficial effects may be linked to

its potential to modulate signal transduction

pathways

Mitogen Activated Protein Kinases MAPK

pathway Activation of p53 protein

Suppression NF-B and AP-1 through the

inhibition of signaling cascades.


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Neutraceutical Questions

Efficacy vs side effects Which is best?? Foods, supplements, or pure

form

Effects of processing? Thermal treatment hasnegative affects

Development of Pharma-foods ?


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Resveratrol BioavailabilityIn cell culture:

Good passive absorption Trans piceid absorption rate limiting

Converted to sulfate form in the cells

In vivo Ethanol does not affect absorption

Side effects with high oral dose

Interaction with blood thinners No proof of positive effect in clinical

studies

controling lipid oxidation

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